Spatially selective nerve stimulation in high-frequency nerve conduction block and recruitment

ABSTRACT

A method of providing therapy to a patient using at least one electrode is provided. The patient has a neural tissue region that is relatively close to the at least one electrode, and a neural tissue region that is relatively far from the at least one electrode. The method comprises conveying time-varying electrical energy from the electrode(s) into the relatively close and far neural tissue regions, wherein the electrical energy has a frequency and amplitude that blocks stimulation of the relatively close neural tissue region, while stimulating the relatively far neural tissue region.

RELATED APPLICATION

The present application claims the benefit under 35 U.S.C. §119 to U.S.provisional patent application Ser. No. 61/218,297, filed Jun. 18, 2009.The foregoing application is hereby incorporated by reference into thepresent application in its entirety.

FIELD OF THE INVENTION

The present inventions relate to tissue stimulation systems, and moreparticularly, to systems and methods for adjusting the stimulationprovided to tissue to optimize a therapeutic effect.

BACKGROUND OF THE INVENTION

Implantable neurostimulation systems have proven therapeutic in a widevariety of diseases and disorders. Pacemakers and Implantable CardiacDefibrillators (ICDs) have proven highly effective in the treatment of anumber of cardiac conditions (e.g., arrhythmias). Spinal CordStimulation (SCS) systems have long been accepted as a therapeuticmodality for the treatment of chronic pain syndromes, and theapplication of tissue stimulation has begun to expand to additionalapplications, such as angina pectoris and incontinence. Deep BrainStimulation (DBS) has also been applied therapeutically for well over adecade for the treatment of refractory Parkinson's Disease, and DBS hasalso recently been applied in additional areas, such as essential tremorand epilepsy. Further, in recent investigations, Peripheral NerveStimulation (PNS) systems have demonstrated efficacy in the treatment ofchronic pain syndromes and incontinence, and a number of additionalapplications are currently under investigation. Furthermore, FunctionalElectrical Stimulation (FES) systems such as the Freehand system byNeuroControl (Cleveland, Ohio) have been applied to restore somefunctionality to paralyzed extremities in spinal cord injury patients.

Each of these implantable neurostimulation systems typically includesone or more electrode carrying stimulation leads, which are implanted atthe desired stimulation site, and a neurostimulator implanted remotelyfrom the stimulation site, but coupled either directly to thestimulation lead(s) or indirectly to the stimulation lead(s) via a leadextension. Thus, electrical pulses can be delivered from theneurostimulator to the stimulation electrode(s) to stimulate or activatea volume of tissue in accordance with a set of stimulation parametersand provide the desired efficacious therapy to the patient. A typicalstimulation parameter set may include the electrodes that are sourcing(anodes) or returning (cathodes) the stimulation current at any giventime, as well as the amplitude, duration, and rate of the stimulationpulses. The neurostimulation system may further comprise a handheldpatient programmer to remotely instruct the neurostimulator to generateelectrical stimulation pulses in accordance with selected stimulationparameters. The handheld programmer in the form of a remote control (RC)may, itself, be programmed by a clinician, for example, by using aclinician's programmer (CP), which typically includes a general purposecomputer, such as a laptop, with a programming software packageinstalled thereon.

When stimulating neural tissue, the order in which nerve fibers areelectrically stimulated or activated (i.e., the neural recruitmentorder), which is governed by spatial and morphometric criteria, has beena known issue that can limit efficacy by resulting in side effects(e.g., dorsal root stimulation, motor fiber stimulation,non-root-related effects, such as temperature, proprioceptor, reflex arcnerves, etc) that preclude the programming of stimulation systems torecruit fibers that could have possibly increased efficacy of thetherapy.

For example, the neural recruitment order may be correlated to thediameter of the nerve fibers that innervate the volume of tissue to bestimulated. In SCS, activation (i.e., recruitment) of large diametersensory fibers is believed to reduce/block transmission of smallerdiameter pain fibers via interneuronal interaction in the dorsal horn ofthe spinal cord. Activation of large sensory fibers also creates asensation known as paresthesia that can be characterized as analternative sensation that replaces the pain signals sensed by thepatient.

Because larger nerve fibers have lower stimulation thresholds thansmaller nerve fibers, the larger nerve fibers will normally bestimulated before smaller nerve fibers when located the same distancefrom the active electrode or electrodes. Because of this,over-stimulation of nerve fibers closest to the active electrode(s) isoften unavoidable, thereby leading to uncomfortable, intense sensationsin unwanted areas, and in the case of SCS, preventing the recruitment ofdeeper and/or smaller nerve fibers that might increase the efficacy ofthe therapy.

Thus, a neurostimulation system that could modify the recruitment orderwith respect to depth of nerve fibers, such that deeper nerve fibers arerecruited more preferentially than shallower nerve fibers, would bevaluable to “tune” the desired therapeutic effect of a neurostimulationapplication, such as SCS.

SUMMARY OF THE INVENTION

In accordance with the present inventions, a method of providing therapyto a patient using at least one electrode is provided. The patient has aneural tissue region that is relatively close to the electrode(s), and aneural tissue region that is relatively far from the electrode(s). Therelatively close neural tissue region results in a side-effect whenstimulated to a particular degree, and the relatively far neural tissueregion results in therapy when stimulated. The method comprisesconveying time-varying electrical energy (e.g., sinusoidal) from theelectrode(s) into the relatively close and far neural tissue regions.The electrical energy has a frequency and amplitude that blocksstimulation of the relatively close neural tissue region, whilestimulating the relatively far neural tissue region. In one method, thetime-varying electrical energy is generated using a hybrid of multiplefrequencies. In another method, the relatively close neural tissueregion and the relative far neural tissue region are located in thespinal cord of the patient. In this case, the relatively close neuraltissue region may comprise superficial dorsal column nerve fibers, andthe relatively far neural tissue region comprises non-superficial dorsalcolumn nerve fibers.

Other and further aspects and features of the invention will be evidentfrom reading the following detailed description of the preferredembodiments, which are intended to illustrate, not limit, the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate the design and utility of preferred embodimentsof the present invention, in which similar elements are referred to bycommon reference numerals. In order to better appreciate how theabove-recited and other advantages and objects of the present inventionsare obtained, a more particular description of the present inventionsbriefly described above will be rendered by reference to specificembodiments thereof, which are illustrated in the accompanying drawings.Understanding that these drawings depict only typical embodiments of theinvention and are not therefore to be considered limiting of its scope,the invention will be described and explained with additionalspecificity and detail through the use of the accompanying drawings inwhich:

FIG. 1 is plan view of one embodiment of a spinal cord stimulation (SCS)system arranged in accordance with the present inventions;

FIG. 2 is a plan view of the SCS system of FIG. 1 in use with a patient;

FIG. 3 is a plan view of an implantable pulse generator (IPG) and oneembodiment of a stimulation lead used in the SCS system of FIG. 1;

FIG. 4 is a block diagram of the internal components of the IPG of FIG.3;

FIG. 5 is a diagram illustrating the blocking of a nerve fiber usinghigh frequency electrical energy;

FIG. 6 is a bar graph illustrating the blocking depths and activationdepths of nerve fibers plotted against the amplitude of high frequencyelectrical energy generated by a neurostimulator used in the system ofFIG. 1; and

FIG. 7 is a bar graph illustrating the blocking depths and activationdepths of nerve fibers plotted against the frequency of high frequencyelectrical energy generated by a neurostimulator used in the system ofFIG. 1.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The description that follows relates to a spinal cord stimulation (SCS)system. However, it is to be understood that the while the inventionlends itself well to applications in SCS, the invention, in its broadestaspects, may not be so limited. Rather, the invention may be used withany type of implantable electrical circuitry used to stimulate tissue.For example, the present invention may be used as part of a pacemaker, adefibrillator, a cochlear stimulator, a retinal stimulator, a stimulatorconfigured to produce coordinated limb movement, a cortical stimulator,a deep brain stimulator, peripheral nerve stimulator, microstimulator,or in any other neural stimulator configured to treat urinaryincontinence, sleep apnea, shoulder sublaxation, headache, etc.

Turning first to FIG. 1, an exemplary SCS system 10 generally includesone or more (in this case, two) implantable stimulation leads 12, animplantable neurostimulator 14, an external remote controller RC 16, aclinician's programmer (CP) 18, an External Trial Stimulator (ETS) 20,and an external charger 22.

The neurostimulator 14 is physically connected via one or morepercutaneous lead extensions 24 to the stimulation leads 12, which carrya plurality of electrodes 26 arranged in an array. In the illustratedembodiment, the stimulation leads 12 are percutaneous leads, and to thisend, the electrodes 26 are arranged in-line along the stimulation leads12. In alternative embodiments, the electrodes 26 may be arranged in atwo-dimensional pattern on a single paddle lead. As will be described infurther detail below, the neurostimulator 14 includes pulse generationcircuitry that delivers the electrical stimulation energy in the form ofa time-varying waveform in accordance with a set of stimulationparameters.

The ETS 20 may also be physically connected via the percutaneous leadextensions 28 and external cable 30 to the stimulation leads 12. The ETS20, which has similar pulse generation circuitry as the neurostimulator14, also delivers electrical stimulation energy to the electrode array26 accordance with a set of stimulation parameters. The major differencebetween the ETS 20 and the neurostimulator 14 is that the ETS 20 is anon-implantable device that is used on a trial basis after thestimulation leads 12 have been implanted and prior to implantation ofthe neurostimulator 14, to test the responsiveness of the stimulationthat is to be provided.

The RC 16 may be used to telemetrically control the ETS 20 via abi-directional RF communications link 32. Once the neurostimulator 14and stimulation leads 12 are implanted, the RC 16 may be used totelemetrically control the neurostimulator 14 via a bi-directional RFcommunications link 34. Such control allows the neurostimulator 14 to beturned on or off and to be programmed with different stimulationparameter sets. The neurostimulator 14 may also be operated to modifythe programmed stimulation parameters to actively control thecharacteristics of the electrical stimulation energy output by theneurostimulator 14. The CP 18 provides clinician detailed stimulationparameters for programming the neurostimulator 14 and ETS 20 in theoperating room and in follow-up sessions. The CP 18 may perform thisfunction by indirectly communicating with the neurostimulator 14 or ETS20, through the RC 16, via an IR communications link 36. Alternatively,the CP 18 may directly communicate with the neurostimulator 14 or ETS 20via an RF communications link (not shown). The external charger 22 is aportable device used to transcutaneously charge the neurostimulator 14via an inductive link 38. Once the neurostimulator 14 has beenprogrammed, and its power source has been charged by the externalcharger 22 or otherwise replenished, the neurostimulator 14 may functionas programmed without the RC 16 or CP 18 being present.

For purposes of brevity, the details of the RC 16, CPS 18, ETS 20, andexternal charger 22 will not be described herein. Details of exemplaryembodiments of these devices are disclosed in U.S. Pat. No. 6,895,280,which is expressly incorporated herein by reference.

As shown in FIG. 2, the electrode lead 12 is implanted within the spinalcolumn 42 of a patient 40. The preferred placement of the electrode lead12 is adjacent, i.e., resting upon, the spinal cord area to bestimulated. Due to the lack of space near the location where theelectrode leads 12 exit the spinal column 42, the neurostimulator 14 isgenerally implanted in a surgically-made pocket either in the abdomen orabove the buttocks. The neurostimulator 14 may, of course, also beimplanted in other locations of the patient's body. The lead extension24 facilitates locating the neurostimulator 14 away from the exit pointof the electrode leads 12. As there shown, the CP 18 communicates withthe neurostimulator 14 via the RC 16.

Referring now to FIG. 3, the external features of the stimulation leads12 and the neurostimulator 14 will be briefly described. One of thestimulation leads 12 has eight electrodes 26 (labeled E1-E8), and theother stimulation lead 12 has eight electrodes 26 (labeled E9-E16). Theactual number and shape of leads and electrodes will, of course, varyaccording to the intended application. The neurostimulator 14 comprisesan outer case 50 for housing the electronic and other components(described in further detail below), and a connector 52 to which theproximal ends of the stimulation leads 12 mate in a manner thatelectrically couples the electrodes 26 to the internal electronics(described in further detail below) within the outer case 50. The outercase 50 is composed of an electrically conductive, biocompatiblematerial, such as titanium, and forms a hermetically sealed compartmentwherein the internal electronics are protected from the body tissue andfluids. In some cases, the outer case 50 may serve as an electrode.

As briefly discussed above, the neurostimulator 14 includes circuitrythat delivers the electrical stimulation energy to the electrode array26 in accordance with a set of stimulation parameters programmed intothe neurostimulator 14. Such stimulation parameters may compriseelectrode combinations, which define the electrodes that are activatedand turned off (zero), percentage of stimulation energy assigned to eachelectrode (fractionalized electrode configurations), and electricalparameters, which define the pulse amplitude (measured in milliamps orvolts depending on whether the neurostimulator 14 supplies constantcurrent or constant voltage to the electrode array 26), and frequency(measured in Hertz).

Turning next to FIG. 4, the main internal components of theneurostimulator 14 will now be described. The neurostimulator 14includes stimulation output circuitry 60 configured for generatingelectrical stimulation energy in accordance with a defined waveformhaving a specified amplitude and frequency control of control logic 62over data bus 64. Control of the frequency of the electrical waveform isfacilitated by timer logic circuitry 66, which may have a suitableresolution, e.g., 10 μs. The stimulation energy generated by the analogoutput circuitry 60 is output via capacitors C1-C16 to electricalterminals 68 corresponding to the electrodes 26.

In the preferred embodiment, the analog output circuitry 60 comprisesindependently controlled current sources for providing stimulationpulses of a specified and known amperage to or from the electricalterminals 68, although in alternative embodiments, the analog outputcircuitry 60 may comprise independently controlled voltage sources forproviding stimulation pulses of a specified and known voltage at theelectrical terminals 68. The operation of this analog output circuitry,including alternative embodiments of suitable output circuitry forperforming the same function of generating stimulation pulses of aprescribed amplitude and width, is described more fully in U.S. Pat.Nos. 6,516,227 and 6,993,384, which are expressly incorporated herein byreference.

The neurostimulator 14 further comprises monitoring circuitry 70 formonitoring the status of various nodes or other points 72 throughout theneurostimulator 14, e.g., power supply voltages, temperature, batteryvoltage, and the like. The monitoring circuitry 70 is also configuredfor measuring electrical parameter data (e.g., electrode impedanceand/or electrode field potential). The neurostimulator 14 furthercomprises processing circuitry in the form of a microcontroller (μC) 74that controls the control logic 62 over data bus 76, and obtains statusdata from the monitoring circuitry 70 via data bus 78. Theneurostimulator 14 further comprises memory 80 and oscillator and clockcircuit 82 coupled to the microcontroller 74. The microcontroller 74, incombination with the memory 80 and oscillator and clock circuit 82, thuscomprise a microprocessor system that carries out a program function inaccordance with a suitable program stored in the memory 80.Alternatively, for some applications, the function provided by themicroprocessor system may be carried out by a suitable state machine.

Thus, the microcontroller 74 generates the necessary control and statussignals, which allow the microcontroller 74 to control the operation ofthe neurostimulator 14 in accordance with a selected operating programand stimulation parameters. In controlling the operation of theneurostimulator 14, the microcontroller 74 is able to individuallygenerate stimulation energy at the electrical terminals 68 using theanalog output circuitry 60, in combination with the control logic 62 andtimer logic circuitry 66. The microcontroller 74 facilitates the storageof electrical parameter data measured by the monitoring circuitry 70within memory 80.

The neurostimulator 14 further comprises a receiving coil 84 forreceiving programming data (e.g., the operating program and/orstimulation parameters) from the external programmer (i.e., the RC 16 orCP 18) in an appropriate modulated carrier signal, and charging, andcircuitry 86 for demodulating the carrier signal it receives through thereceiving coil 84 to recover the programming data, which programmingdata is then stored within the memory 80, or within other memoryelements (not shown) distributed throughout the neurostimulator 14.

The neurostimulator 14 further comprises back telemetry circuitry 88 anda transmission coil 90 for sending informational data to the externalprogrammer. The back telemetry features of the neurostimulator 14 alsoallow its status to be checked. For example, when the CP 18 initiates aprogramming session with the neurostimulator 14, the capacity of thebattery is telemetered, so that the CP 18 can calculate the estimatedtime to recharge. Any changes made to the current stimulus parametersare confirmed through back telemetry, thereby assuring that such changeshave been correctly received and implemented within the implant system.Moreover, upon interrogation by the CP 18, all programmable settingsstored within the neurostimulator 14 may be uploaded to the CP 18.

The neurostimulator 14 further comprises a rechargeable power source 92and power circuits 94 for providing the operating power to theneurostimulator 14. The rechargeable power source 92 may, e.g., comprisea lithium-ion or lithium-ion polymer battery or other form ofrechargeable power. The rechargeable source 92 provides an unregulatedvoltage to the power circuits 94. The power circuits 94, in turn,generate the various voltages 96, some of which are regulated and someof which are not, as needed by the various circuits located within theneurostimulator 14. The rechargeable power source 92 is recharged usingrectified AC power (or DC power converted from AC power through othermeans, e.g., efficient AC-to-DC converter circuits, also known as“inverter circuits”) received by the receiving coil 84.

To recharge the power source 92, the external charger 22 (shown in FIG.1), which generates the AC magnetic field, is placed against, orotherwise adjacent, to the patient's skin over the implantedneurostimulator 14. The AC magnetic field emitted by the externalcharger induces AC currents in the receiving coil 84. The charging andforward telemetry circuitry 86 rectifies the AC current to produce DCcurrent, which is used to charge the power source 92. While thereceiving coil 84 is described as being used for both wirelesslyreceiving communications (e.g., programming and control data) andcharging energy from the external device, it should be appreciated thatthe receiving coil 84 can be arranged as a dedicated charging coil,while another coil, such as the coil 90, can be used for bi-directionaltelemetry.

Additional details concerning the above-described and other IPGs may befound in U.S. Pat. No. 6,516,227, U.S. Patent Publication No.2003/0139781, and U.S. patent application Ser. No. 11/138,632, entitled“Low Power Loss Current Digital-to-Analog Converter Used in anImplantable Pulse Generator,” which are expressly incorporated herein byreference.

It should be noted that rather than an IPG, the SCS system 10 mayalternatively utilize an implantable receiver-stimulator (not shown)connected to the stimulation leads 12. In this case, the power source,e.g., a battery, for powering the implanted receiver, as well as controlcircuitry to command the receiver-stimulator, will be contained in anexternal controller inductively coupled to the receiver-stimulator viaan electromagnetic link. Data/power signals are transcutaneously coupledfrom a cable-connected transmission coil placed over the implantedreceiver-stimulator. The implanted receiver-stimulator receives thesignal and generates the stimulation in accordance with the controlsignals.

Significant to the present inventions, the neurostimulator 14 may beoperated in a manner that blocks the stimulation of nerve fibersrelatively close to the active electrode(s) and stimulates nerve fibersthat are relatively far from the active electrode(s). In particular, theneurostimulation 14 generates and conveys high frequency electricalenergy from the active electrode(s) to the relatively close and farnerve fibers. A conventional neural fiber modeling technique shows thathigh frequency electrical energy (greater than 2.2 kHz) blocksstimulation of a nerve fiber at a certain threshold.

For example, with reference to FIG. 5, high frequency electrical energyhaving a zero-mean 5 KHz sinusoidal waveform was applied from anelectrode to a modeled 11.5 μm diameter nerve fiber. During theapplication of the high frequency electrical energy, a test pulse trainwas applied to the end of the modeled nerve fiber. As shown, actionpotentials (measured as the membrane voltage Vm1) generated by the testpulse train were blocked at nodes close to the high frequency electrode(measured as the membrane voltage Vm2), and therefore, could notpropagate toward the other end of the nerve fiber (measured as themembrane voltage Vm3).

Significantly, the blocking threshold of a nerve fiber by high frequencyelectrical energy is higher than the threshold at which the nerve fiberis activated by the same high frequency electrical energy. Thus, if thehigh frequency electrical energy has an amplitude that is higher thanthe blocking threshold of superficial dorsal column nerve fibers, thenon-superficial dorsal nerve fibers at a particular depth will stillhave a blocking threshold above the amplitude of the high frequencyelectrical energy, but a stimulation threshold below the amplitude ofthe high frequency electrical energy. This means that superficial dorsalcolumn nerve fibers will be blocked at a stimulation current thatactivates non-superficial dorsal column fibers.

For example, with reference to FIG. 6, nerve fiber blocking andstimulation as a function of high frequency electrical energy amplitudewas modeled for 11.5 μm diameter nerve fibers on the midline of a spinalcord dorsal column area. As shown, for a relatively low amplitude (2.4mA), nerve fibers up to 400 μm deep into the dorsal column were allstimulated. As the amplitude of the high frequency electrical energy wasincreased (4.8 mA), the blocking threshold of the superficial nervefibers was exceeded, such that nerve fibers up to a depth of 100 μm wereblocked, while the depth of the stimulated nerve fibers was increased toa range of 100-1100 μm. As the amplitude of the high frequencyelectrical energy was further increased (7.0 mA), the depth of theblocked nerve fibers was increased to 400 μm, while the depth of theactivated nerve fibers was increased to a range of 400-1400 μm. Furtherincreasing the amplitude of the high frequency electrical energy (10 mA)further increased the depth of the blocked nerve fibers to 700 μm andfurther increased the depth of the stimulation nerve fibers to a rangeof 700-1800 μm. Thus, it can be appreciated the desired depth range ofblocked nerve fibers and the desired depth range of the stimulationnerve fibers may be tuned by selecting the amplitude of the highfrequency electrical energy.

The desired depth range of blocked nerve fibers and the desired depthrange of the stimulation nerve fibers may be tuned by also selecting thefrequency of the electrical energy. For example, as shown in FIG. 7,using a 2.4 mA amplitude for the high frequency stimulation energy, thedepth of the blocked nerve fibers was up to 200 μm, and the depth of thestimulated nerve fibers was in the range of 200 μm-800 μm for afrequency of 5 KHz. The depth of the blocked nerve fibers was up to 300μm, and the depth of the stimulated nerve fibers was in the range of 300μm-700 μm for a frequency of 6.9 KHz. The depth of the blocked nervefibers was up to 200 μm, and the depth of the stimulated nerve fiberswas in the range of 200 μm-700 μm for a frequency of 14 KHz.

The desired depth range of blocked nerve fibers and the desired depthrange of the stimulation nerve fibers may also be tuned by using hybridsinusoidal waveforms that have been created by combining sinusoidalwaveforms of two different frequencies. For example, as shown in FIG. 7,a 6.9 kHz hybrid sinusoidal waveform was created by combining halfphases of 5 kHz and 14 kHz. As illustrated, the depth ranges of therespective blocked nerve fibers and the stimulation nerve fibersresulting from the 6.9 kHz hybrid sinusoidal waveform are different fromthe depth ranges of the respective blocked nerve fibers and thestimulation nerve fibers resulting from the pure 5 kHz, 6.9 kHz, and 14kHz sinusoidal waveforms. Notably, the ratio between the blocked andstimulated nerve fiber depth is lowest using the hybrid sinusoidalwaveform. Notably, if it is desired to minimize the activated region(which implies greater nerve selectivity), a hybrid sinusoidal waveform(6.9K) is preferred, because it blocks nerve fibers as deep as would atypical 6.9 kHz sinusoidal waveform, but activates nerve fibers lessdeep than would a typical 6.9 kHz sinusoidal waveform. Theneurostimulator 14 may generate the hybrid sinusoidal waveform inresponse to an input from the user (e.g., via the RC 16 or CP 18) of thetwo frequencies that are to be mixed to generate the hybrid sinusoidalwaveform.

Thus, it can be appreciated that by controlling the depth at which nervefibers are both blocked and stimulated, the dorsal column nerve fibersrelatively close to the activate electrode(s), which presumably willcreate an adverse side-effect if stimulated, can be blocked, whereas thedorsal column nerve fibers relatively far from the active electrode(s),which presumably will provide the necessary therapy if stimulated, canbe activated.

Although particular embodiments of the present inventions have beenshown and described, it will be understood that it is not intended tolimit the present inventions to the preferred embodiments, and it willbe obvious to those skilled in the art that various changes andmodifications may be made without departing from the spirit and scope ofthe present inventions. Thus, the present inventions are intended tocover alternatives, modifications, and equivalents, which may beincluded within the spirit and scope of the present inventions asdefined by the claims.

What is claimed is:
 1. A method of providing therapy to a patient usingat least one electrode, the patient having a neural tissue region thatis relatively close to the at least one electrode, and a neural tissueregion that is relatively far from the at least one electrode, themethod comprising: conveying time-varying electrical energy from the atleast one electrode into the relatively close and far neural tissueregions, wherein the electrical energy has a frequency and amplitudethat blocks stimulation of the relatively close neural tissue region,while stimulating the relatively far neural tissue region, wherein therelatively close neural tissue region results in a side-effect whenstimulated, and the relatively far neural tissue region results intherapy when stimulated.